Apraxia of speech due to the left postcentral gyrus lesion.

Key Clinical Message: Apraxia of speech (AOS) due to a postcentral infarction differs from conventional precentral AOS with respect to phonemic errors (phoneme substitution) which are more common than phonetic errors (phoneme distortion) and preserved accent and intonation. Abstract: Clinical features of apraxia of speech caused by lesions in the postcentral gyrus have not yet been elucidated. Here, we report a patient with this lesion and show how postcentral apraxia of speech differs from the hitherto known precentral apraxia of speech. A 54-year-old man developed Broca's aphasia with apraxia of speech that resolved into pure apraxia of speech within 3 weeks following infarction of the postcentral gyrus. The diagnosis of apraxia of speech was based on the patient's effortful, slow speech and inconsistent phonetic distortions with phonemic paraphasia. The Western Aphasia Battery was used to examine the patient's speech samples. Speech was recorded using a digital voice recorder and transcribed into a narrow transcription of the International Phonetic Alphabet. The error types were categorized phonologically. The results revealed that (a) phonemic errors (vowel and consonant substitutions, also known as phonemic paraphasia) were more common than phonetic errors (vowel and consonant distortions). Similar to conduction aphasia, phonemic errors were more pronounced in confrontation naming than in repetition, accompanied by self-correction, and (b) word accent and sentence intonation were preserved, although the speech was slow. These two features are characteristic of postcentral apraxia of speech, which can be differentiated from conventional precentral apraxia of speech.

Ventral Variant Posterior Cortical Atrophy with Occipito-temporal Accumulation of Tau Proteins/Astrocyte Gliosis.

A 73-year-old woman with posterior cortical atrophy (PCA) presented with progressive apperceptive visual agnosia, alexia, agraphia, ventral simultanagnosia, prosopagnosia, and allocentric (stimulus-centered) left-sided hemispatial neglect. All of these symptoms were attributed to damage to the bilateral occipito-temporal cortices, consistent with ventral variant PCA. While the Pittsburgh compound B uptake was extensively distributed throughout the occipito-parietal (dorsal) and occipito-temporal (ventral) areas, the THK5351 (ligand binding to tau aggregates/astrocyte gliosis) accumulation was limited to the ventral area. These findings suggest that local accumulation of tau proteins and/or astrocyte gliosis over the occipito-temporal cortices can result in ventral variant PCA.

Tactually-related cognitive impairments: sharing of neural substrates across associative tactile agnosia, agraphesthesia, and kinesthetic reading difficulty.

INTRODUCTION: A precise understanding of the neural substrates underlying tactually-related cognitive impairments such as bilateral tactile agnosia, bilateral agraphesthesia, kinesthetic alexia and kinesthetic reading difficulty is currently incomplete. In particular, recent data have implicated a role for the lateral occipital tactile visual region, or LOtv, in tactile object naming (Amedi et al. Cerebral Cortex 2002). Thus, this study set out to examine the degree to which the LOtv may be involved in tactually-related cognitive impairments by examining two unique cases. METHODS: To assess whether LOtv or the visual word form area (VWFA) is involved in tactually-related cognitive impairments, the average activation point of LOtv and that of VWFA were placed on the single-photon emission computed tomography (SPECT) cerebral blood flow images of two patients: one with bilateral associative tactile agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading, and the other with kinesthetic reading difficulty. RESULTS: The average LOtv coordinate was involved in the area of hypoperfusion in both patients, whereas that of VWFA was not included in any of the hypoperfused areas. CONCLUSIONS: The results support the view that interruption of LOtv or disconnection to LOtv and to VWFA may cause these tactually-related cognitive impairments. Further, bilateral associative tactile agnosia and bilateral agraphesthesia are attributable toward the damage of the occipital lobe, whereas unilateral or predominantly one-sided associative tactile agnosia and agraphesthesia are attributable toward the damage of the parietal lobe.

Anomia with Amnesia Caused by Hemorrhage in the Left Anterior and Medial Thalamus: Thalamic Anomia Particularly for Artificial Objects.

We herein report the case of a patient who showed pure anomia and amnesia caused by hemorrhage in the left thalamus, involving the anterior, ventral anterior, and mediodorsal nuclei. It was revealed that the anomia was characterized by impaired retrieval of object names, which was more pronounced in artificial objects, and abundant perseveration, whereas the amnesia was mild and limited to daily routine events, which was made clear from the results of an episodic memory scale. Detailed lesion localization and literature review revealed that a combination of pure anomia and amnesia can occur in a lesion involving the anterior, ventral anterior, or mediodorsal nucleus of the thalamus. The relative specificity to artificial objects can be explained by the locally damaged fiber connection to the putative category-specific lexical area in the temporal lobe.

On-Reading (Chinese-Style Pronunciation) Predominance Over Kun-Reading (Native Japanese Pronunciation) in Japanese Semantic Dementia.

Japanese kanji (morphograms) have two ways of reading: on-reading (Chinese-style pronunciation) and kun-reading (native Japanese pronunciation). It is known that some Japanese patients with semantic dementia read kanji with on-reading but not with kun-reading. To characterize further reading impairments of patients with semantic dementia, we analyzed data from a total of 9 patients who underwent reading and writing tests of kanji and kana (Japanese phonetic writing) and on-kun reading tests containing two-character kanji words with on-on reading, kun-kun reading, and specific (so-called Jukujikun or irregular kun) reading. The results showed that on-reading preceding (pronouncing first with on-reading) and kun-reading deletion (inability to recall kun-reading) were observed in nearly all patients. In the on-kun reading test, on-reading (57.6% correct), kun-reading (46.6% correct), and specific-reading (30.0% correct) were more preserved in this decreasing order (phonology-to-semantics gradient), although on-reading and kun-reading did not significantly differ in performance, according to a more rigorous analysis after adjusting for word frequency (and familiarity). Furthermore, on-substitution (changing to on-reading) errors in kun-reading words (27.0%) were more frequent than kun-substitution (changing to kun-reading) errors in on-reading words (4.0%). These results suggest that kun-reading is more predominantly disturbed than on-reading, probably because kun-reading and specific-reading are closely associated with the meaning of words.

Asymmetric Bálint's syndrome with multimodal agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading due to subcortical hemorrhage in the left parieto-occipito-temporal area.

We report a patient with asymmetric Bálint's syndrome (predominantly right-sided oculomotor apraxia and simultanagnosia and optic ataxia for the right hemispace), and multimodal agnosia (apperceptive visual agnosia and bilateral associative tactile agnosia) with accompanying right hemianopia, bilateral agraphesthesia, hemispatial neglect, global alexia with unavailable kinesthetic reading, and lexical agraphia for kanji (Japanese morphograms), after hemorrhage in the left parieto-occipito-temporal area. The coexistence of tactile agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading suggests that tactile-kinesthetic information can be interrupted because of damage to the fiber connection from the parietal lobe to the occipito-temporal area, leading to these tactually related cognitive impairments.

Antibodies to the α3 subunit of the ganglionic-type nicotinic acetylcholine receptors in patients with autoimmune encephalitis.

Since autonomic dysfunction is closely associated with autoimmune encephalitis (AE), the objective of this study was to determine the autonomic symptoms and the prevalence of anti-α3 subunit of the ganglionic-type nicotinic acetylcholine receptor (gAChRα3) antibodies in the patients with AE. We reviewed the clinical features of 19 AE patients, and specifically analyzed sera for anti-gAChRα3 antibodies using the luciferase immunoprecipitation system (LIPS) assay. Cardiovascular autonomic symptoms were found to be common in patients with AE, and hypersalivation was seen only in patients with NMDAR encephalitis. LIPS detected anti-gAChRα3 antibodies in the sera from patients with AE (5/29, 26%). This study is the first to demonstrate that clinical characteristics including autonomic symptoms of AE patients with seropositivity for gAChR autoantibodies. It will be important to verify the role of gAChR antibodies in autonomic dysfunction and brain symptoms to clarify the pathogenesis of AE.

Dorsal type letter-by-letter reading accompanying alexia with agraphia due to a lesion of the lateral occipital gyri.

We report a patient with alexia with agraphia accompanied by letter-by-letter reading after hemorrhage in the left middle and inferior occipital gyri that spared the angular gyrus and the fusiform gyrus. Kanji (Japanese morphograms) and kana (Japanese phonetic writing) reading and writing tests revealed that alexia with agraphia was characterized by kana-predominant alexia and kanji-predominant agraphia. This type of "dorsal" letter-by-letter reading is discernable from conventional ventral type letter-by-letter reading that is observed in pure alexia in that (1) kinesthetic reading is less effective, (2) kana or literal agraphia coexists, and (3) fundamental visual discrimination is nearly normal.

Selective impairment of On-reading (Chinese-style pronunciation) in alexia with agraphia for kanji due to subcortical hemorrhage in the left posterior middle temporal gyrus.

We report a patient with alexia with agraphia for kanji after hemorrhage in the left posterior middle temporal gyrus. The results of single-character kanji reading and two-character on- (Chinese-style pronunciation), kun- (native Japanese pronunciation), and Jukujikun (irregular kun-) reading word tests revealed that the patient could not read kanji characters with on-reading but read the characters with kun-reading. We consider that this on-reading alexia was caused by disconnection between the posterior inferior temporal cortex (orthographic lexicon) and the posterior superior temporal gyrus (phonological lexicon), and preserved kun- and Jukujikun-reading was realized by bypassing the orthography-to-phonology route by the semantic route.

Progressive Supranuclear Palsy with Wall-Eyed Bilateral Internuclear Ophthalmoplegia Syndrome: Authors' Second Case.

Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome has previously been reported in only 2 patients with progressive supranuclear palsy (PSP). Herein, we report a third case of WEBINO syndrome with PSP. The patient was an 81-year-old man who had experienced gradually increasing gait disturbance and occasional falls since the age of 78 years. At 80 years of age, he presented with cognitive impairment, parkinsonism, and oculomotor abnormalities. The oculomotor abnormalities consisted of vertical gaze palsy and loss of eye convergence. Brain magnetic resonance imaging demonstrated marked atrophy of the midbrain. He was diagnosed with PSP. At the age of 81 years, he presented with alternating extropia in his forward gaze and adduction paresis and outward nystagmus of the abducted eye in his horizontal gaze, both of which were compatible with WEBINO syndrome. Previously, we reported the first case of PSP with WEBINO syndrome, and another group recently reported a second case. In light of the previous cases and the present case, WEBINO syndrome in PSP should not be considered extremely rare. Furthermore, WEBINO syndrome has not been reported in other neurodegenerative disorders, which suggests that it might be a useful and specific diagnostic finding in PSP.

Kanji (Morphogram) and Kana (Phonogram) Problem in Japanese Alexia and Agraphia.

The kanji and kana (or kanji vs. kana) problem in the Japanese language denotes the dissociation between kanji (morphograms) and kana (phonograms) in reading/comprehension and writing. Since paragraphia of kana in a patient with amyotrophic lateral sclerosis was first reported in 1893, kanji-kana dissociation has been the central topic in Japanese aphasiology. Recent advancements in lesion-to-symptom analyses and functional imaging studies have identified some areas whose damage causes dissociative disturbances of reading or writing between kanji and kana. That is, (1) angular alexia with agraphia causes kanji agraphia; alexia of kana with an angular gyrus lesion is the result of a damage to the middle occipital gyrus; (2) alexia with agraphia for kanji is caused by a posterior inferior temporal cortex (mid-fusiform/inferior temporal gyri; visual word form area) lesion, whereas pure agraphia for kanji is caused by a posterior middle temporal gyrus lesion; and (3) pure alexia, particularly for kanji, results from a mid-fusiform gyrus lesion (Brodmann's Area [BA] 37), whereas pure alexia for kana results from a posterior fusiform/inferior occipital gyri lesion (BA 18/19).

Rapidly progressive miliary brain metastasis of lung cancer after EGFR tyrosine kinase inhibitor discontinuation: An autopsy report.

Miliary brain metastasis is a rare type of brain metastasis, in which carcinoma cells disseminate to numerous foci confined to Virchow-Robin/subpial spaces. Symptoms usually progress within several months, and magnetic resonance imaging (MRI) shows multiple small contrast-enhancing lesions. We report an autopsy case of a patient who rapidly deteriorated within a week due to miliary brain metastasis after epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) discontinuation, without contrast-enhancing lesions on MRI. A 74-year-old woman was diagnosed with stage IV lung adenocarcinoma with EGFR L868R mutation 2 years before presentation. Gefitinib, an EGFR-TKI was started. After 7 months, multiple new punctate contrast-enhancing lesions in the cerebral cortex appeared. After switching to another EGFR-TKI, erlotinib, these lesions disappeared. One year later, erlotinib was discontinued because of disease progression in the lung and docetaxel was initiated. Sixteen days later, cognitive decline appeared which rapidly progressed to bedridden state in 4 days. MRI showed multiple cortical small fluid-attenuated inversion recovery high intensity lesions which lacked contrast enhancement. The patient exhibited a state of akinetic mutism within a few days, and died 52 days after the appearance of neurological symptoms. The rapid progression indicated disease flare after EGFR-TKI discontinuation. Autopsy revealed numerous foci of metastasis in the cerebral cortex, basal ganglia, thalamus, and cerebellum, in which cancer cells were mostly confined to the Virchow-Robin/subpial spaces. These pathological findings were compatible with previous reports of miliary brain metastasis. Recent reports suggest that early disseminated cancer cells can survive for a long time and even remain after chemotherapy in supportive niches, and Virchow-Robin spaces are the niches in the brain. Our case suggests that these cancer cells may rapidly proliferate as a withdrawal burst after discontinuation of molecular targeted drugs, and show pathological findings of miliary brain metastasis.

Inflammatory myopathy with myasthenia gravis: Thymoma association and polymyositis pathology.

Objective: To provide evidence that idiopathic inflammatory myopathy (IM) with myasthenia gravis (MG) frequently shows thymoma association and polymyositis (PM) pathology and shares clinicopathologic characteristics with IM induced by immune checkpoint inhibitors (ICIs). Methods: We analyzed the clinicopathologic features of 10 patients with idiopathic IM and MG identified in 970 consecutive patients with biopsy-proven IM. Results: Seven patients (70%) had thymoma. IM and MG were diagnosed with more than 5-year time difference in 6 thymomatous patients and within 1 year in 1 thymomatous and 3 nonthymomatous patients. Seven thymomatous patients showed rhabdomyolysis-like features with respiratory failure (4/7), dropped head (3/7), cardiac involvement (2/7), and positive anti-acetylcholine receptor (anti-AChR) and anti-titin antibodies (7/7 and 4/6, respectively) but rarely showed ocular symptoms (2/7) or decremental repetitive nerve stimulation (RNS) responses (1/7) at IM diagnosis. Three nonthymomatous patients showed acute cardiorespiratory failure with rhabdomyolysis-like features (1/3), positive anti-AChR and anti-titin antibodies (3/2 and 2/2, respectively), and fluctuating weakness of the skeletal muscle without ocular symptoms (3/3). Muscle pathology showed a PM pathology with infiltration of CD8-positive CD45RA-negative T-lymphocytes (9/9), scattered endomysial programmed cell death 1 (PD-1)-positive cells (9/9), and overexpression of programmed cell death ligand 1 (PD-L1) on the sarcolemma of muscle fibers around the infiltrating PD-1-positive cells (7/9). Conclusion: Rhabdomyolysis-like features, positive anti-AChR antibody without decremental RNS responses, and PD-L1 overexpression are possible characteristics shared by ICI-induced IM. Frequent thymoma association in patients with idiopathic IM and MG may suggest thymoma-related immunopathogenic mechanisms, including dysregulation of the immune checkpoint pathway.

An Autopsy Case of Familial Neuronal Intranuclear Inclusion Disease with Dementia and Neuropathy.

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease with marked variety in its clinical manifestations. While characteristic neuroimaging and skin biopsy findings are important clues to the diagnosis, autopsy studies are still important for confirming the exact disease features. We herein report the case of a patient who received an antemortem diagnosis of familial NIID with dementia-dominant phenotype that was later confirmed by an autopsy. Our report is the first to document a case of autopsy-confirmed NIID involving both cognitive impairment and sensorimotor neuropathy.

Frontal Phonological Agraphia and Acalculia with Impaired Verbal Short-Term Memory due to Left Inferior Precentral Gyrus Lesion.

We report a patient with phonological agraphia (selective impairment of kana [Japanese phonetic writing] nonwords) and acalculia (mental arithmetic difficulties) with impaired verbal short-term memory after a cerebral hemorrhage in the opercular part of the left precentral gyrus (Brodmann area 6) and the adjacent postcentral gyrus. The patient showed phonemic paragraphia in five-character kana nonword writing, minimal acalculia, and reduced digit and letter span. Mental arithmetic normalized after 8 months and agraphia recovered to the normal range at 1 year after onset, in parallel with an improvement of the auditory letter span score from 4 to 6 over a period of 14 months and in the digit span score from 6 to 7 over 24 months. These results suggest a close relationship between the recovery of agraphia and acalculia and the improvement of verbal short-term memory. The present case also suggests that the opercular part of the precentral gyrus constitutes the phonological route in writing that conveys phonological information of syllable sequences, and its damage causes phonological agraphia and acalculia with reduced verbal short-term memory.

Asymmetric oculomotor apraxia, optic ataxia, and simultanagnosia with right hemispatial neglect from a predominantly left-sided lesion of the parieto-occipital area.

INTRODUCTION: Bálint's syndrome involves bilateral damage to the parieto-occipital area. The extent of the effect of unilateral damage on the Bálint's triad (oculomotor apraxia, optic ataxia, and simultanagnosia) remains unknown. METHODS: We examined a 63-year-old, right-handed woman who developed right hemianopia, oculomotor apraxia, optic ataxia, simultanagnosia, and hemispatial neglect (HSN) for the right after a cerebral infarction, with detailed neuropsychological tests, magnetic resonance imaging, and single photon emission computed tomography (SPECT). RESULTS: Neuropsychological examination showed that oculomotor apraxia, optic ataxia, and simultanagnosia were more pronounced in the right hemi-space, probably due to the limited eye movement in the right visual field, whereas HSN was restricted to the right hemi-space. Diffusion-weighted MR images revealed hyperintensity in the left parieto-temporo-occipital region, and several spotty areas of the bilateral frontal and parietal subcortical regions. SPECT revealed hypoperfusion in the left parieto-occipital region and frontal operculum and small areas of the right superior parietal lobule. CONCLUSIONS: The case suggests that asymmetric (more pronounced in the right hemi-space) oculomotor apraxia, optic ataxia, and simultanagnosia occur in an extensive lesion of the left parieto-occipital cortices. Although HSN is not a prerequisite for simultanagnosia, the coexistence of HSN aggravates simultanagnosia in the hemi-space opposite the lesion.

High PR3-ANCA positivity in a patient with chronic inflammatory demyelinating polyneuropathy.

Proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) is reported to be highly specific to vasculitis compared to myeloperoxidase (MPO)-ANCA. We report a case of a 19-year-old woman with chronic inflammatory demyelinating polyneuropathy (CIDP) with high PR3-ANCA positivity. The patient responded well to intravenous immunoglobulin plus oral steroid, and showed no signs of systemic vasculitis during the subsequent 10 months of follow-up. Our present case suggests that CIDP may accompany high PR3-ANCA levels, which should be differentiated from axonal neuropathy due to vasculitis.

Progressive Bálint's Syndrome in a Patient Demonstrating Dementia with Lewy Bodies.

We herein report a 65-year-old man demonstrating dementia with Lewy bodies who first presented with Bálint's syndrome. Two years later, a mild cognitive impairment was noted. From three years after onset, he developed progressive parkinsonism, visual hallucination, and autonomic dysfunction, in line with the deterioration of the cognitive function. Single photon emission computed tomography with a 99mTc-ethylcysteinate dimer performed two years after onset revealed hypoperfusion in the restricted area of the bilateral superior parietal lobule, which extended to the lateral occipital cortices within two years. It is suggested that the pathological process can extend from the parietal to occipital lobes.

[Brodmann Areas 39 and 40: Human Parietal Association Area and Higher Cortical Function].

The anatomy and function of the angular gyrus (Brodmann Area 39) and supramarginal gyrus (Brodmann Area 40) are described here. Both gyri constitute the inferior part of the parietal lobe. Association fibers from the angular gyrus project to the dorsolateral prefrontal cortex via the superior longitudinal fasciculus (SLF) II/arcuate fasciculus (AF), whereas those from the supramarginal gyrus project to the ventrolateral prefrontal cortex via SLF III/AF. Damage to the left angular gyrus causes kanji agraphia (lexical agraphia) and mild anomia, whereas damage to the left supramarginal gyrus causes kana alexia (phonological dyslexia) and kana agraphia (phonological agraphia). Damage to either gyrus causes Gerstmann's syndrome (finger agnosia, left-right disorientation, agraphia and acalculia) and verbal short-term memory impairment. "Angular alexia with agraphia" results from damage to the middle occipital gyrus posterior to the angular gyrus. Alexia and agraphia, with lesions in the angular or supramarginal gyrus, are characterized by kana transposition errors in reading words, which suggests the impairment of sequential phonological processing.